{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:12:26Z","timestamp":1783163546830,"version":"3.54.6"},"reference-count":28,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["FIS PI18\/00205"],"award-info":[{"award-number":["FIS PI18\/00205"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["PI21\/00231"],"award-info":[{"award-number":["PI21\/00231"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish MPN group (GEMFIN) for NGS","award":["FIS PI18\/00205"],"award-info":[{"award-number":["FIS PI18\/00205"]}]},{"name":"Spanish MPN group (GEMFIN) for NGS","award":["PI21\/00231"],"award-info":[{"award-number":["PI21\/00231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Myelofibrosis (MF) is a heterogeneous disease regarding its mutational landscape, clinical presentation, and outcomes. The aim of our work is to evaluate the genomic classification of MF considering whether it is primary or secondary. One-hundred seventy-five patients, 81 with primary MF (PMF) and 94 with secondary MF (SMF) were hierarchically allocated into eight molecular groups. We found that TP53 disruption\/aneuploidy (n = 16, 9%) was more frequent (12% versus 6%) and showed higher allele burden (57% versus 15%, p = 0.01) in SMF than in PMF, and was associated with shorter survival (median 3.5 years). Mutations in chromatin\/spliceosome genes (n = 72, 41%) represented the most frequent genomic group in PMF. Homozygous JAK2 mutation (n = 40, 23%) was enriched with old patients with SMF after long-standing polycythemia vera, whereas MF with heterozygous JAK2 mutation (n = 22, 13%) was similarly distributed among PMF and SMF. MF with CALR mutation (n = 19, 11%) predominated in post-essential thrombocythemia MF. The remaining genomic groups were infrequent. TP53 disruption, chromatin\/spliceosome mutation, and homozygous JAK2 mutation were associated with significantly shorter survival and higher risk of progression. In conclusion, genomic classification reveals different pathogenic pathways between PMF and SMF and provides relevant information regarding disease phenotype and outcomes.<\/jats:p>","DOI":"10.3390\/cancers15153904","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:24:24Z","timestamp":1690881864000},"page":"3904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Characteristics and Outcomes of Patients with Primary and Secondary Myelofibrosis According to the Genomic Classification Using Targeted Next-Generation Sequencing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-1466","authenticated-orcid":false,"given":"Marta","family":"Garrote","sequence":"first","affiliation":[{"name":"Hematopathology Section, Pathology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-0178","authenticated-orcid":false,"given":"M\u00f3nica","family":"L\u00f3pez-Guerra","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Pathology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-7826","authenticated-orcid":false,"given":"Eduardo","family":"Arellano-Rodrigo","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Rozman","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Pathology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Carbonell","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6376-0929","authenticated-orcid":false,"given":"Francesca","family":"Guijarro","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Pathology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Santaliestra","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari Mutua Terrassa, 08221 Terrassa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Triguero","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8484","authenticated-orcid":false,"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Pathology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Medicine Campus, Faculty of Medicine and Health Sciences, Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"\u00c1lvarez-Larr\u00e1n","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Cl\u00ednic Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1182\/blood-2014-07-575373","article-title":"How I treat myelofibrosis","volume":"124","author":"Cervantes","year":"2014","journal-title":"Blood"},{"key":"ref_2","first-page":"152","article-title":"Clinico-biological characteristics of patients with myelofibrosis: An analysis of 1000 cases from the Spanish Registry of Myelofibrosis","volume":"155","author":"Correa","year":"2020","journal-title":"Med. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41375-018-0077-1","article-title":"Philadelphia chromosome-negative classical myeloproliferative neoplasms: Revised management recommendations from European LeukemiaNet","volume":"32","author":"Barbui","year":"2018","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1182\/blood-2014-05-578435","article-title":"Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis","volume":"124","author":"Rumi","year":"2014","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/leu.2016.351","article-title":"Driver mutations\u2019 effect in secondary myelofibrosis: An international multicenter study based on 781 patients","volume":"31","author":"Passamonti","year":"2017","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/leu.2014.343","article-title":"CALR mutation, MPL mutation and triple negativity identify patients with the lowest vascular risk in primary myelofibrosis","volume":"29","author":"Finazzi","year":"2015","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/s41375-020-0979-6","article-title":"Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide","volume":"35","author":"Chowdhury","year":"2021","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1038\/leu.2013.119","article-title":"Mutations and prognosis in primary myelofibrosis","volume":"27","author":"Vannucchi","year":"2013","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1056\/NEJMoa1716614","article-title":"Classification and Personalized Prognosis in Myeloproliferative Neoplasms","volume":"379","author":"Grinfeld","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/gcc.22789","article-title":"Targeted molecular characterization shows differences between primary and secondary myelofibrosis","volume":"59","author":"Courtier","year":"2020","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1182\/blood-2008-07-170449","article-title":"New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment","volume":"113","author":"Cervantes","year":"2009","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1038\/leu.2017.169","article-title":"A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis","volume":"31","author":"Passamonti","year":"2017","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.ijbiomac.2019.07.065","article-title":"Roles of T875N somatic mutation in the activity, structural stability of JAK2 and the transformation of OCI-AML3 cells","volume":"137","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s12185-019-02725-8","article-title":"Essential thrombocytosis attributed to JAK2-T875N germline mutation","volume":"110","author":"Yoshimitsu","year":"2019","journal-title":"Int. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1182\/bloodadvances.2021006350","article-title":"ASXL1 mutations are prognostically significant in PMF, but not MF following essential thrombocythemia or polycythemia vera","volume":"6","author":"Guglielmelli","year":"2022","journal-title":"Blood Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1200\/JCO.2017.76.4886","article-title":"MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients with Primary Myelofibrosis","volume":"36","author":"Guglielmelli","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1200\/JCO.2018.78.9867","article-title":"MIPSS70+ Version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis","volume":"36","author":"Tefferi","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41375-018-0107-z","article-title":"GIPSS: Genetically inspired prognostic scoring system for primary myelofibrosis","volume":"32","author":"Tefferi","year":"2018","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1182\/bloodadvances.2020003444","article-title":"Genomic analysis of primary and secondary myelofibrosis redefines the prognostic impact of ASXL1 mutations: A FIM study","volume":"5","author":"Riou","year":"2021","journal-title":"Blood Adv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1182\/bloodadvances.2020002175","article-title":"RAS\/CBL mutations predict resistance to JAK inhibitors in myelofibrosis and are associated with poor prognostic features","volume":"4","author":"Coltro","year":"2020","journal-title":"Blood Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ajh.26648","article-title":"SF3B1 mutations in primary and secondary myelofibrosis: Clinical, molecular and prognostic correlates","volume":"97","author":"Loscocco","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/ajh.24978","article-title":"Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN alliance study of 1,095 patients","volume":"93","author":"Tefferi","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1182\/blood-2014-07-588426","article-title":"The prognostic advantage of calreticulin mutations in myelofibrosis might be confined to type 1 or type 1-like CALR variants","volume":"124","author":"Tefferi","year":"2014","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41408-023-00786-x","article-title":"Phenotypic correlations of CALR mutation variant allele frequency in patients with myelofibrosis","volume":"13","author":"Guglielmelli","year":"2023","journal-title":"Blood Cancer J."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/15\/3904\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:27Z","timestamp":1760127807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/15\/3904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":28,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cancers15153904"],"URL":"https:\/\/doi.org\/10.3390\/cancers15153904","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]}}}